DAVID F. AND MARGARET T. GROHNE FAMILY CANCER IMMUNOLOGY AND IMMUNOTHERAPY PROGRAM PROJECT SUMMARY The Cancer Immunology and Immunotherapy (CII) Program is a longstanding basic and translational sciences program within the Mayo Clinic Cancer Center (MCCC). In 2016, this program was officially endowed by the David F. and Margaret T. Grohne Family. The Program continues to work toward better understanding the mechanisms of immunity, the relationship between inflammation and cancer, and the development of innovative solutions to combat cancer through immune therapy. The CII Program has contributed significantly to checkpoint blockade therapy, which has resulted in a major change in the standard of care of several different cancers. It is now poised to make additional major contributions such as using antibody-targeted chemotherapeutics, effectively targeting melanoma and ovarian cancers, which have proven nonresponsive to established therapies. The Program includes 35 members, representing 14 different departments in the Mayo Clinic College of Medicine and Science. The current membership is a historically highly productive team with a total publication record in excess of 5000 papers that has garnered over 245,000 citations. The main goal of the Program is to provide an interactive, supportive, and durable scientific environment to foster our four principal cutting-edge Specific Aims: (1) To develop new knowledge about how the immune system functions, (2) To develop novel antibody-based therapies for the treatment of cancers (3) To identify and develop vaccine approaches that can be implemented to protect against cancer recurrence and improve the efficacy of immune modulation with checkpoint inhibitors, and (4) To develop innovative strategies to redirect non-tumor antigen- specific T cells to attack cancer. The CII Program has been consistently well-funded and currently is supported by extramural peer-reviewed grants totaling $3.6M in direct costs of which ~35% are from NCI. Direct funding from non-peer-reviewed grants is $8.4M resulting in an overall total of $12M. This is a 20% increase over the last funding period. In the 2013-2017 timeframe, Program members published 650 cancer-related publications, of which 19% were intraprogrammatic, 57% were interprogrammatic, and 124 were published in journals with impact factors ?10, reflecting the quality of the work and illustrating the high degree of interaction the CII Program members have with members of other MCCC Programs.